PROJECT SUMMARY Chronic wounds including diabetic ulcers and decubitus ulcers are a major health concern, but tools to diagnose these wounds before they have erupted or evaluate deep tissue response to therapy have remained elusive. Treatment is more expensive than prevention, but there are few tools to identify early stage disease. Indeed, visual inspection remains the standard of care for detection early stage ulcers, but it cannot map the altered tissue in three dimensions nor can it quantify the aberrant physiology underlying the ulcer. Current approaches to preventing decubitus ulcers are labor-intensive monitoring and repositioning. While pressure- sensitive devices can identify when a pressure threshold has been reached, there is no correlation between amount/duration of pressure and ulcer development. What is missing is information on changes in tissue physiology and not simply a brute metric such as pressure. This work will use photoacoustic ultrasound to create a detailed map of the tissue physiology at the wound site or site of a potential wound. This can then report the exact site needing treatment or how a site is responding to treatment. Our preliminary data showed that we could detect pressure ulcers before they erupted and thus this approach could potentially have significant clinical value. While this preliminary data was for pressure ulcers only, we suggest that this approach will likely have value to both decubitus and diabetic ulcers because signal in photoacoustic ultrasound is based on changes in tissue optical absorption from hemoglobin, and diabetic and decubitus ulcers both have a dysregulated microvasculature. This rationale motivates this study, and the clinical value of the final imaging protocol is a 3D map of the ulcer or potential ulcer below the surface to predict ulcer formation or monitor treatment response. Aim 1 will use a rodent model of diabetic ulcers. We hypothesize that the photoacoustic signal will be higher in untreated animals than treated animals. Aim 2 will image human subjects presenting to the Veterans Administration hospital in San Diego with decubitus ulcers. We will stratify these people as a function of ulcer stage and hypothesize that more advanced stages will have higher photoacoustic ultrasound signal in the wound. The clinical impacts include early detection of both types of ulcers. Ulcers are currently detected based on symptoms?this work will detect them based on physiology. This will also offer three-dimensional imaging. Visual inspection only offers information about the skin surface. Our acoustics approach will map and measure the extent of dysregulation through the first 5 cm of tissue. This will be particularly useful in monitoring a treatment response because areas of low response can be prioritized for additional treatment.